RAGE signaling by alveolar macrophages influences tobacco smoke-induced inflammation

Robinson, Adam B.; Johnson, KacyAnn D.; Bennion, Brock G.; Reynolds, Paul

doi:10.1152/ajplung.00099.2012

Cited by 59 publications

(43 citation statements)

References 56 publications

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“…The siRNA inhibition of RAGE expression decreased CSE-induced NFkB activation and cytokine secretion (Reynolds et al, 2011). Further evidence indicated that elevated levels of RAGE in alveolar macrophages was accompanied by an increased expression of active Ras and proinflammatory cytokines, which were reduced in RAGE-deficient alveolar macrophages (Robinson et al, 2012b;Chen et al, 2013). Together, these findings suggest that RAGE may mediate the effects of cigarette smoking or CSE on airway and pulmonary inflammation.…”

Section: Discussionmentioning

confidence: 89%

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Cheng²,

Ma³

et al. 2014

DNA and Cell Biology

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The receptor for advanced glycation end products (RAGE) is a cell surface molecule of the immunoglobulin superfamily that binds diverse endogenous ligands involved in the development of chronic diseases and inflammatory damage. A growing body of evidence has suggested that RAGE is involved in the development and progression of chronic obstructive pulmonary disease (COPD). The present study investigated the existence of an association among three polymorphisms (-374T/A, -429T/C, and G82S) of the RAGE gene with the risk of COPD in the Chinese population. The RAGE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism in 216 patients with COPD and 239 age-matched healthy individuals. Our study demonstrated that the frequencies of the GS genotype and the S allele in the G82S mutation were significantly higher in COPD patients than in controls (odds ratios [OR]=1.70, 95% confidence interval [CI]: 1.15-2.50, p=0.0098 and OR=1.42, 95% CI: 1.06-1.91, p=0.023, respectively). Further stratification analysis by smoking status revealed that the presence of the GS genotype conferred a higher risk of developing COPD in current smokers (p=0.044). In contrast, mutations at -374T/A and -429T/C did not demonstrate any association with COPD, even after taking into account the patients' smoking history. Our study provides preliminary evidence that the G82S polymorphism in the RAGE gene is associated with an increased risk of COPD and that the GS genotype of the G82S variant is a risk factor for COPD in the Chinese population.

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Section: Discussionmentioning

confidence: 89%

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Cheng²,

Ma³

et al. 2014

DNA and Cell Biology

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“…Epithelial cells were also found to produce substantial numbers of MVs, but with delayed kinetics compared with alveolar macrophages. It has been previously suggested that epithelial cell-derived MVs are upregulated in BALF in patients with ARDS at 6 hours after intubation for respiratory failure,12 although these MVs were identified by expression of the receptor for advanced glycation end products (RAGE), and would likely represent a mixture of cell origins as various lung cells express RAGE 34. CD11b + /Ly6G + MVs were only apparent at 4 hours in our model of LPS-induced ALI, suggesting that these are MVs produced by infiltrating neutrophils.…”

Section: Discussionmentioning

confidence: 99%

Alveolar macrophage-derived microvesicles mediate acute lung injury

Soni

Wilson

O’Dea

et al. 2016

Thorax

167

185

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BackgroundMicrovesicles (MVs) are important mediators of intercellular communication, packaging a variety of molecular cargo. They have been implicated in the pathophysiology of various inflammatory diseases; yet, their role in acute lung injury (ALI) remains unknown.ObjectivesWe aimed to identify the biological activity and functional role of intra-alveolar MVs in ALI.MethodsLipopolysaccharide (LPS) was instilled intratracheally into C57BL/6 mice, and MV populations in bronchoalveolar lavage fluid (BALF) were evaluated. BALF MVs were isolated 1 hour post LPS, assessed for cytokine content and incubated with murine lung epithelial (MLE-12) cells. In separate experiments, primary alveolar macrophage-derived MVs were incubated with MLE-12 cells or instilled intratracheally into mice.ResultsAlveolar macrophages and epithelial cells rapidly released MVs into the alveoli following LPS. At 1 hour, the dominant population was alveolar macrophage-derived, and these MVs carried substantive amounts of tumour necrosis factor (TNF) but minimal amounts of IL-1β/IL-6. Incubation of these mixed MVs with MLE-12 cells induced epithelial intercellular adhesion molecule-1 (ICAM-1) expression and keratinocyte-derived cytokine release compared with MVs from untreated mice (p<0.001). MVs released in vitro from LPS-primed alveolar macrophages caused similar increases in MLE-12 ICAM-1 expression, which was mediated by TNF. When instilled intratracheally into mice, these MVs induced increases in BALF neutrophils, protein and epithelial cell ICAM-1 expression (p<0.05).ConclusionsWe demonstrate, for the first time, the sequential production of MVs from different intra-alveolar precursor cells during the early phase of ALI. Our findings suggest that alveolar macrophage-derived MVs, which carry biologically active TNF, may play an important role in initiating ALI.

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“…The elastin mRNA expression can be induced by the TGF-␤ receptor/ Smad signaling pathway and stabilized by the active protein kinases p38 and/or PKC␦ (11,27). Out of these factors p38 was reported to be involved in RAGE signaling (7,42,50). Therefore, it is well conceivable that sRAGE/RAGE contributes to higher elastin levels via p38 action.…”

Section: Discussionmentioning

confidence: 99%

The receptor for advanced glycation end-products supports lung tissue biomechanics

Al‐Robaiy

Weber

Simm

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. Since RAGE acts as a cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function in a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult, and old RAGE knockout (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability, and inflammatory parameters (TNF-␣, high-mobility group box protein 1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or cocultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.receptor for advanced glycation end-products; aging; biomechanics; elastin; mouse THE RECEPTOR FOR ADVANCED glycation end-products (RAGE) is a pattern recognition receptor of the immunoglobulin superfamily (32). RAGE is predominantly expressed in lung, particularly in the type I alveolar epithelial (ATI) cells (12,15,46). This specific localization suggests its important physiological function in the alveolar epithelium. In other cell types and tissues, the expression of RAGE is activated in response to pathophysiological conditions, such as the accumulation of advanced glycation end-products (AGEs) and inflammation (1). RAGE expression is highly associated with lung development and increases during the alveolarization (29,40). High RAGE expression prior to the alveolarization period has adverse effects associated with a severe pulmonary dysplasia (16,41). A reduced alveolar expression of RAGE is related to pathophysiological changes of the lung tissue, such as carcinoma (3), fibrosis (34, 37), and chronic obstructive pulmonary disease (COPD) (34). In addition to the membrane-bound receptor, soluble RAGE (sRAGE) forms exist as the result of either alternative splicing (22) or protein shedding by metalloproteinases (39, 52). sRAGE normally exists in the bronchoalveolar lavage (BAL) at a high level (53), but it is deficient in neutrophilic asthma and COPD (47, 49).The physiological importance of RAGE in lung is not yet fully understood because mice lacking RAGE do not show obvious pulmonary alterations (5, 9). Only intervention studies indicated an adverse effect of RAGE in the development of lung fibrosis (14, 19) and acute lung injury (4...

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RAGE signaling by alveolar macrophages influences tobacco smoke-induced inflammation

Cited by 59 publications

References 56 publications

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Association of Polymorphisms of the Receptor for Advanced Glycation End Products Gene with COPD in the Chinese Population

Alveolar macrophage-derived microvesicles mediate acute lung injury

The receptor for advanced glycation end-products supports lung tissue biomechanics

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